The goal of our research is to determine the mechanism by which the phosphate diester cyclic AMP activates a protein kinase from bovine brain which we have succeeded in isolating and purifying. One hypothesis, based on model studies, for the binding of cyclic AMP to enzymes which we plan to test is that this six-membered cyclic phosphate diester acts as a reversible adenylylating agent. If this hypothesis proves to be correct in the case of bovine brain protein kinase, we shall carry out experiments to identify the amino acid to which the phosphoryl group of cyclic AMP becomes attached in the adenylylation process as well as any residues which assist the formation of the cyclic AMP-enzyme complex. In addition to the studies on the binding to and activation of the enzyme by cyclic AMP, we intend to initiate a mechanistic study of the process by which the enzyme catalyzes phosphate transfer from ATP to protein acceptors. In numerous diseases, including cancer-related ones, changes occur in the regulation of the concentration of cyclic AMP. If we succeed in elucidating the mechanism by which cyclic AMP affects the action of our enzyme, our results are likely to have broad implications for the understanding of the role of cyclic AMP in a variety of biological phenomena, including cancer.